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Data from Synergy of Topical Toll-like Receptor 7 Agonist with Radiation and Low-Dose Cyclophosphamide in a Mouse Model of Cutaneous Breast Cancer
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Data from Synergy of Topical Toll-like Receptor 7 Agonist with Radiation and Low-Dose Cyclophosphamide in a Mouse Model of Cutaneous Breast Cancer
Data from Synergy of Topical Toll-like Receptor 7 Agonist with Radiation and Low-Dose Cyclophosphamide in a Mouse Model of Cutaneous Breast Cancer
MD
M. Zahidunnabi Dewan
M. Zahidunnabi Dewan
CV
Claire Vanpouille-Box
Claire Vanpouille-Box
NK
Noriko Kawashima
Noriko Kawashima
SD
Sara DiNapoli
Sara DiNapoli
JB
James S. Babb
James S. Babb
SF
Silvia C. Formenti
Silvia C. Formenti
SA
Sylvia Adams
Sylvia Adams
SD
Sandra Demaria
Sandra Demaria
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31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1078-0432.c.6522203.v1
Abstract
Purpose: This study tested the hypothesis that topical Toll-like receptor (TLR) 7 agonist imiquimod promotes antitumor immunity and synergizes with other treatments in a model of skin-involving breast cancer.Experimental Design: TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice. Imiquimod 5% or placebo cream was applied topically on the shaved skin overlying tumors three times/wk. In some experiments, local ionizing radiation therapy (RT) was delivered to the tumor in three fractions of 8 Gy, given on consecutive days. Cyclophosphamide was given intraperitoneally (i.p.) in one dose of 2 mg/mouse. Mice were followed for tumor growth and survival.Results: Treatment with imiquimod significantly inhibited tumor growth, an effect that was associated with increased tumor infiltration by CD11c+, CD4+, and CD8+ cells, and abolished by depletion of CD8+ cells. Administration of imiquimod in combination with RT enhanced significantly tumor response compared with either treatment alone (P < 0.005), and 11% to 66% of irradiated tumors completely regressed. Importantly, the addition of topical imiquimod also resulted in growth inhibition of a secondary tumor outside of the radiation field. Low-dose cyclophosphamide given before start of treatment with imiquimod and RT further improved tumor inhibition and reduced tumor recurrence. Mice that remained tumor-free rejected a tumorigenic inoculum of TSA cells, showing long-term immunologic memory.Conclusions: Topical imiquimod inhibits tumor growth and synergizes with RT. Addition of cyclophosphamide further increases the therapeutic effect and induces protective immunologic memory, suggesting that this combination is a promising strategy for cutaneous breast cancer metastases. Clin Cancer Res; 18(24); 6668–78. ©2012 AACR.
Keywords
SYNERGIZES
LOW DOSE CYCLOPHOSPHAMIDE
RADIATION
TREATMENT WITH IMIQUIMOD
CUTANEOUS
BREAST CANCER
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